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Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Retrospective and open-label trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. There is a need to clarify the evidence available in the form of randomised controlled trials for its use in bipolar disorder.To review the evidence for the efficacy and acceptability of topiramate in the treatment of acute mood episodes in bipolar disorder.The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group search strategy was used. The following databases were searched:The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), September 2003;The Cochrane Controlled Clinical Trials Register (CCCTR), September 2003;EMBASE (1980 to December 2003);MEDLINE (1966 to December 2003);LILACS;PsycLIT;Psyndex.Reference lists of relevant papers and major textbooks of mood disorder. Handsearches (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials.Randomised controlled trials which compared topiramate with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder. Participants were patients with bipolar disorder and were males and females of all ages.Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean difference was used for continuously distributed outcomes.One randomised controlled trial met the inclusion criteria for the review, a comparison between topiramate and bupropion sustained release (SR) in the adjunctive treatment of depressed patients with bipolar disorder. However, the trial had several limitations in methodology and in the description of data. Its data regarding efficacy required clarification before it could be analysed according to the protocol of this systematic review. From the limited data available, topiramate had efficacy similar to bupropion SR in the adjunctive treatment of bipolar depression. Both groups of subjects suffered a high drop-out rate. There was no significant difference between the topiramate and the bupropion treated groups in those dropping out for any reason (relative risk 1.60, 95% confidence interval 0.65 to 3.96). There was no significant difference in those withdrawing from the study due to adverse effects (relative risk 1.50, 95% confidence interval 0.51 to 4.43). Although the data on weight loss were not analysed formally, weight loss was marked in the topiramate treated group. Several unpublished trials have been identified and data from these trials may be included in future reviews.There is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness, either in monotherapy or as an adjunctive treatment.

The paper draws on a number of Grid projects, particularly on the experience of NeuroGrid, a UK project in the Neurosciences tasked with developing a Grid-based collaborative research environment to support the sharing of digital images and patient data across multiple distributed sites. It outlines recurrent socio-technical issues, highlighting the challenges of scaling up technological networks in advance of the regulatory networks which normally regulate their use in practice.

BACKGROUND: Tiagabine, an anticonvulsant, has been reported to have efficacy in prophylactic treatment of bipolar disorder in case reports and in case series. OBJECTIVES: To review the efficacy and acceptability of tiagabine, relative to placebo, and other agents in the prevention and/or attenuation of episodes of bipolar affective disorder. The efficacy and acceptability of tiagabine were considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of affective disorder were examined.Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Specialist journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomised controlled trials which compare tiagabine with placebo, alternative mood stabilisers or antipsychotics, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder, were sought. Bipolar patients, male and female, of all ages were to be included. DATA COLLECTION AND ANALYSIS: Data were to be extracted from the original reports if they met our inclusion criteria. The main outcomes to be assessed were:(1) The efficacy of tiagabine treatment in preventing or attenuating further episodes of bipolar affective disorder, including its efficacy in rapid cycling disorder.(2) The acceptability of tiagabine treatment to patients.(3) The prevalence of side effects.(4) Mortality, if any, on tiagabine treatment.Outcomes concerning relapse or recurrence were to be analysed excluding data from studies using discontinuation protocols, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of tiagabine treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were to be analysed using Review Manager version 4.2.8. MAIN RESULTS: No randomised controlled trials of tiagabine in the maintenance treatment of bipolar disorder were found. AUTHORS' CONCLUSIONS: There is an insufficient methodologically rigorous evidence base to provide guidance on the use of tiagabine in the maintenance treatment of bipolar disorder. There is a need for randomised controlled trials examining the therapeutic potential of this agent in bipolar disorder, after the nature of reported episodes of syncope or seizure in tiagabine-treated bipolar patients has been established.

Summary Background We aimed to review published work for the efficacy and safety of electroconvulsive therapy (ECT) with simulated ECT, ECT versus pharmacotherapy, and different forms of ECT for patients with depressive illness. Methods We designed a systematic overview and metaanalysis of randomised controlled trials and observational studies. We obtained data from the Cochrane Collaboration Depressive Anxiety and Neurosis and Schizophrenia Group Controlled trial registers, Cochrane Controlled Trials register, Biological Abstracts, CINAHL, EMBASE, LILACS, MEDLINE, PsycINFO, and SIGLE, reference lists, and specialist textbooks. Our main outcome measures were depressive symptoms, measures of cognitive function, and mortality. Findings Meta-analysis of data of short-term efficacy from randomised controlled trials was possible. Real ECT was significantly more effective than simulated ECT (six trials, 256 patients, standardised effect size [SES] ‐0·91, 95% CI ‐1·27 to ‐0·54). Treatment with ECT was significantly more effective than pharmacotherapy (18 trials, 1144 participants, SES ‐0·80, 95% CI ‐1·29 to ‐0·29). Bilateral ECT was more effective than unipolar ECT (22 trials, 1408 participants, SES ‐0·32, 95% CI ‐0·46 to ‐0·19). Interpretation ECT is an effective short-term treatment for depression, and is probably more effective than drug therapy. Bilateral ECT is moderately more effective than unilateral ECT, and high dose ECT is more effective than low dose.

We were interested to read J. J. Hutchinson and A. Puranik (1992) on journal clubs at St Edward's Hospital, and would like to share our experience of running journal clubs in Sheffield. As stated, the College does not provide guidelines on the format of journal clubs, but they do provide a suggested reading list. While this contains interesting and relevant papers, it does not provide a good basis for a journal club programme.

A laboratory animal model empolying thermal lesions was developed to demonstrate that re-entrant activity made possible by prolongation of conduction time could be enhanced by shortening of recovery properties. Cooling was used to prolong conduction time and warming to shorten recovery time. The cardiac cycle was scanned with premature stimuli of three times diastolic threshold intensity. Re-entrant activity could not be elicited in the presence of shortened recovery times alone. However, abbreviation of recovery time enhanced re-entrant activity, permitting re-entrant beats to occur during a greater period of the cardiac cycle, and to occur at cold temperatures that, when present alone were not associated with re-entry. During some re-entrant beats, right preceded left ventricular activation despite evidence that re-entrant activity originated in the left ventricle in the area of the cold-spot. This was an unexpected finding and suggested that the Purkinje net played a role in the re-entrant loop. The findings of this study indicate that, while prolongation of conduction time is necessary for re-entrant activity, it is enhanced by shortening of recovery times. Both of these electrophysiologic features are present in the early phases of acute myocardial infarction and may be a factor in the very high incidence of ventricular ectopic activity at that time

The early time course of vulnerability of the ventricles to fibrillation after coronary artery occlusion was measured in 6 dogs. The duration of a train of 60 Hz stimuli with currents of 2 to 3 times the diastolic threshold was used as the measure of vulnerability to fibrillation. Within 2 minutes of coronary occlusion the duration of the train of 60 Hz stimuli inducing fibrillation fell by an average of 25 percent of control values. Five minutes after coronary occlusion the duration of the train was an average of 34 percent shorter than control values. In all animals, the duration of the train required to produce fibrillation began to increase 30 minutes after coronary occlusion and approached control values. The relation of these findings to the time course of arrhythmias in experimental infarction and the early high mortality rate in cases of infarction in man is discussed.

I AM of opinion that the phenomena referred to by Mr. Hossack are not the effect of waterspouts, but are rather to be attributed to landslips. I may mention a case which may throw some light on the matter. About 1872 (I cannot give the exact date) a landslip occurred on the banks of the Tay, about seven miles north of Dunkeld, close to Guay Station on the Highland Railway, and on the east side of that line. I lived close by at the time, and shortly afterwards saw the effects. Local opinion attributed it to the following causes:—Along the top of the gravelly slope planted with oak and other trees, ran a brook. Immediately above the place where the landslip occurred, the banks of the brook had been burrowed by rabbits. When the sudden flood occurred which caused the landslip, the water of the brook entered these holes, undermined the gravelly slope or terraced beach, and precipitated it across the highway into the field below, devastating fully an acre of it. The trees, turf, &c., were deposited in the field much as they grew upon the slope. I was surprised that they had not been overturned, but it would appear that they had slid down. The effects are still quite visible to passengers on the railway. Had they been photographed at the time, they would have formed a capital illustration for a geological text-book.